In South Africa, young people have the highest incidence of HIV infection in the general population. Adolescence is a complex, transitional development phase when behaviors associated with HIV acquisition are often initiated, and it is likely that any current or future HIV prevention strategy will need to be effectively utilized by young people to have an appreciable population-level impact. But despite the importance of HIV prevention efforts among young people, there are few interventions that have demonstrated a significant impact in reducing risk of HIV infection among this group in South Africa and other resource-limited settings. This project will address this gap through a novel approach to combining different HIV prevention strategies into an optimized prevention 'menu'for adolescents, from which young women and men at risk of HIV infection may choose a particular combination of strategies to meet their specific needs and circumstances. Currently there are a number of promising and proven prevention interventions that could potentially constitute a prevention menu of preferred options or combinations, including PrEP, microbicides, HIV Counseling and Testing (HCT) and circumcision. After a systematic review of the literature relating to these and other prevention options, pilot studies will be designed in order to examine key issues of feasibility, acceptability, adherence and sexual behavior change associated with these prevention methods in adolescents. Studies will emulate implementation of services and trials as far as possible in order to address these questions, including ethico-legal issues associated with implementation and delivery, as well as consideration of messaging and social marketing of these approaches to adolescents. Results will be used to inform epidemiological modeling and costing exercises in order to inform how such a prevention 'menu'should be constructed and promoted among young people for maximum benefit. This research will culminate in a separately proposed trial to examine the efficacy of the 'menu'approach in preventing new HIV infections among South African adolescents. PUBLIC HEALTH RELEVANCE: The success of this proposal will provide critical information towards improving HIV prevention efforts among adolescents, both in sub-Saharan Africa and globally. The insights generated will have direct applications in enhancing specific HIV prevention interventions and in the design of a robust trial to evaluate a novel approach to combining biological and behavioral prevention modalities.